プロスタグランジン受容体の構造と機能 : 創薬への考察  [in Japanese] STRUCTURES AND FUNCTIONS OF PROSTANOID RECEPTORS  [in Japanese]

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Author(s)

    • 市川 厚 ICHIKAWA Atsushi
    • 京都大学薬学部衛生化学教室 Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University
    • 根岸 学 NEGISHI Manabu
    • 京都大学薬学部衛生化学教室 Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University
    • 杉本 幸彦 SUGIMOTO Yukihiko
    • 京都大学薬学部衛生化学教室 Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University

Abstract

We reviewed the recent advances in the molecular characterization of prostanoid receptors. Prostanoids exert versatile actions in diverse tissues and cells through specific cell surface receptors. Molecular biological studies revealed the primary structure of eight types and subtypes of prostanoid receptors from various species. In mouse, these include the thromboxane A2 receptor (TP), prostacyclin receptor (IP), prostaglandin(PG)F receptor (FP), PGD receptor and four subtypes of PGE receptors (EP1, EP2, EP3 and EP4). In addition, at least three isoforms of PGE receptor EP3 subtype have been identified. They are produced through alternative RNA splicing from a single gene and differ only in their carboxy-terminal tails. These isoforms differ in the efficiency of G protein activation, in the specificity of coupling to G proteins or in sensitivity to desensitization. The IP, EP2, EP4 and DP receptors are coupled to stimulation of adenylate cyclase, the TP, EP1, and FP receptors are coupled to Ca<SUP>2</SUP> mobilization, and EP3 receptors are coupled to inhibition of adenylate cyclase. Sequence homology among these functionally related receptors is higher than that between the two groups, indicating that the functionally related receptors may be localized on the near branches of evolution tree. The conserved sequences of the receptors may involve counter binding sites for the groups of prostanoid structure such as an α-carboxylic acid, a hydroxy group at position 15, and two aliphatic side chains. Among these sequences, the arginine residue in the seventh transmembrane domain, was proposed to be the binding site of the α-carboxylic acid of the prostanoid molecules. The molecular characterization is useful for understanding not only the diverse physiological actions of prostanoids, but the interaction between receptor structure and specific analogue.

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 106, 29-34, 1995-09-01

    The Japanese Pharmacological Society

References:  28

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